case report - Acta Otorhinolaryngologica Italica

ACTA otorhinolaryngologica italica 2011;31:186-189
Case report
Granular cell tumour of the tongue in a 14-year-old
boy: case report
Tumore a cellule granulari della lingua in un paziente di 14 anni: case report
M. Barbieri, Y. Musizzano1, M. Boggio2, C. Carcuscia
ENT Department, University of Genoa; 1 Department of Surgical and Diagnostic Sciences (DISC), Division
of Pathology, University of Genoa; 2 Pathology Unit, Department of Biomedical Laboratory, San Martino University
Hospital, Genoa, Italy
Summary
Granular cell tumour is a rare soft tissue neoplasm that can virtually affect any site of the body. Its histological origin is controversial, since
several studies have shown that different cells are involved. Granular cell tumour was initially described as myoblastoma, but, at present,
a neural origin is supported by most Authors, due to the immunohistochemical pattern. Even if the biological behaviour of granular cell
tumours is usually benign, accurate histological examination is mandatory, because in a small number of cases they can be malignant. Here,
a case is described of granular cell tumour in a 14-year-old boy, which is a very rare occurrence, since these tumours typically manifest in
subjects between the third and sixth decade. Histopathological features, differential diagnosis and therapeutic implications of granular cell
tumour are discussed, together with a brief review of the recent literature.
Key words: Tongue • Granular cell tumour • Abrikossoff • Myoblastoma
Riassunto
Il tumore a cellule granulari (TCG) è una rara neoplasia dei tessuti molli che può interessare ogni sede corporea. La sua istogenesi è
ancora controversa; diversi studi hanno infatti dimostrato il coinvolgimento di differenti linee cellulari. Esso è stato inizialmente definito
“mioblastoma”, ma attualmente molti Autori fanno riferimento ad una probabile origine neurale, sulla base del quadro immunoistochimico. I tumori a cellule granulari sono di natura prevalentemente benigna, ma è sempre necessario eseguire un accurato esame istologico,
perché, seppur solo in rari casi, essi possono manifestare caratteri di malignità. In questo lavoro presentiamo un caso di tumori a cellule
granulari insorto in un paziente di soli 14 anni, evenienza assai rara, considerato che questi tumori si manifestano tipicamente tra la terza
e la sesta decade di vita. Vengono descritti l’aspetto istopatologico, la diagnosi differenziale ed il trattamento della lesione insieme ad una
breve revisione della letteratura recente.
parole chiave: Lingua • Tumore a cellule granulari • Abrikossoff • Mioblastoma
Acta Otorhinolaryngol Ital 2011;31:186-189
Introduction
Granular cell tumour (GCT), or Abrikossoff’s tumour,
first described, in 1926, by the Russian pathologist Alexei
Ivanovich Abrikossoff, represents a rare entity, with a reported prevalence ranging from 0.019% to 0.03% of all human neoplasms 1. It can affect soft tissues virtually in any
body site, and typically manifests in adults between the
third and the sixth decade, usually showing a benign behaviour; women are affected twice as much as men (M/F ratio = 1:2) 2. The histological origin of GCT is controversial,
since different derivations have been postulated by various
Authors, including fibroblasts 3, myoblasts 4, undifferentiated mesenchymal cells, Schwann cells 5, histiocytes 6 and
neural cells 7. Accordingly, different definitions have been
applied to this entity, such as myoblastoma, granular cell
neurofibroma, and granular cell schwannoma.
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The neuroectodermal origin is now generally accepted due
to the reactivity of GCT for neural markers 8, although recent investigations 9, considering large series, demonstrated that the tumour could be regarded as the expression of
local metabolic or reactive changes, rather than as a true
neoplasm; this is demonstrated by the wide variety of features and architectural patterns, as well as by the usually
benign behaviour of GCT. Albeit, in these recent studies,
immunohistochemical reactivity of granular cells to broad
panels, including antibodies directed against different tissues, did not confirm any particular differentiation.
It has been demonstrated that GCTs of the oral cavity can
occur both in paediatric and advanced age, but their incidence usually peaks between the fourth and the sixth decade 10, while their occurrence before the age of 20 years
is very rare 2.
Granular cell tumour of the tongue in a 14-year-old boy
GCT frequently appears as a solitary tumour, but multifocal lesions have also been described 11. Despite the fact
that most of these lesions arise in the cervico-facial region
(up to 50% of GCTs occur in the head and neck 12), only a
few cases have been reported in the oral cavity 13.
Case report
A 14-year-old boy came to our attention with a painless
lingual swelling, incidentally discovered three months
earlier. He did not complain of bleeding, and no significant clinical data (diabetes, hypertension, allergies) were
present in his clinical history; our patient had always been
well and he referred to a healthy lifestyle; laboratory investigations were substantially normal. Physical examination confirmed the presence of a primarily right-seated
mass involving the apex and body of the tongue, and the
patient underwent surgical excision of the tumour, followed by pathological examinations.
The surgical specimen measured 17 × 15 × 4 mm with a
depressed and peripherally ulcerated area about 10 mm
in maximum length; on the cut surface, the ulceration
appeared as a vaguely nodular grey-to-red lesion, with
ill-defined borders. On histological examination, the
lingual epithelium showed marked pseudoepitheliomatous hyperplasia, while in the underlying submucosa a
neoplastic proliferation was observed. Neoplastic cells
were mainly round, with small hyperchromatic nuclei
and abundant granular eosinophilic cytoplasm, strictly
intermingled with bundles of striated muscle and fibrous
tissue, and disposed in nests and sheets of variable size;
the tumour showed infiltrative and ill-defined borders.
Intra-cytoplasmic PAS-positive granules were revealed
by the appropriate histochemical staining. At immunohistochemistry, all neoplastic cells were S-100-positive
and CD68(PGM1)-positive. The proliferation index,
semiquantitatively evaluated with Ki67 (clone K2)-labelling index, was very low, very close to 0%. Surgical
margins were negative.
In conclusion, all histomorphological and immunohistochemical findings were consistent with GCT of the
tongue. The patient was first examined one week later
and then, respectively, 1, 4, 7, 14 and 20 months after the
surgical excision; so far, no sign of recurrence has been
noted. Albeit, further close follow-up has been planned to
assess the effectiveness of the eradication and to prevent
any possible relapse of the disease.
Discussion
GCTs are unusual in the first and second decade, therefore,
in children and adolescents, many other benign lesions
should be considered in the differential diagnosis: amongst
which, minor salivary gland tumours, dermoid cysts, vascular lesions, lipomas, benign mesenchymal neoplasm,
Fig. 1. Pseudo-epitheliomatous hyperplasia of the epithelium (left) underlying
the tumour (right) is a frequent feature associated with GCT; hence, squamous
cell carcinoma should be ruled out in the differential diagnosis (H&E, original
magnification: 100).
neurofibroma and traumatic fibroma 14. Moreover, GCT
often presents as uncapsulated, often as a pseudo-invasive
lesion 15, therefore, even several malignancies, such as squamous carcinoma and malignant melanoma, should be
ruled out, even if they rarely arise in the oral cavity of
young patients. Moreover, in the overlying lingual epithelium various degrees of pseudo-epitheliomatous hyperplasia are frequently seen, and this can mimic squamous
cell carcinoma (Fig. 1); therefore, if incisional biopsy is
performed, it should be deep enough to include underlying infiltrating granular cells 12.
Surgical excisional biopsy of the tumour represents the
first choice, both for diagnosis and treatment and, in the
majority of cases, it is curative; albeit, removal of the lesion should be wide enough to grant oncological radicality,
irrespective of the final histological diagnosis. Upon histological examination, GCT typically shows small nests and
sheets of polygonal cells with small vesicular nuclei and
granular eosinophilic cytoplasm (Fig. 2); the latter is due to
intracytoplasmic accumulation of lysosomes and appears
to be the main morphological feature of GCTs, better seen
in PAS-stained slides 16. Another peculiar finding is S100reactivity, that suggests a neural origin of the tumour; it
should be remembered that granular cell populations have
been described in some non-neural neoplasms of the skin,
including benign fibrous histiocytoma, dermatomyofibroma and cutaneous leiomyosarcoma; albeit, these tumours
are S100-negative, in contrast to the classic GCT 17.
Another rare and recently described entity, sharing common histological features with GCT, is congenital granular cell lesion (CGCL), also known as congenital granular
cell epulis or congenital granular cell tumour. Based on a
recent review, only 7 cases of CGCL of the tongue were
reported in the literature; moreover, differential diagnosis
between GCT and CGCL can be made by immunochemical staining for S-100, that is negative in CGCL and positive in GCT 18.
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M. Barbieri et al.
Fig. 2. Irregular nests and sheets of neoplastic cells were strictly intermingled with bundles of striated muscle and fibrous tissue (H&E, original magnification: 200).
The potential aggressiveness of this tumour should never be overlooked, given the fact that 1-3% of GCTs can
present in a malignant way 19. According to an accurate
AFIP study, histological malignancy should be suggested
by the presence of 3 or more of the following 6 criteria:
1) high mitotic activity (> 2 mitoses/10 fields at 200× magnification); 2) necrosis; 3) high nuclear-cytoplasmic ratio;
4) spindling; 5) vesicular nuclei with large nucleoli; and
6) pleomorphism. Neoplasms featuring only one or two
of the above-mentioned should be diagnosed as “atypical” GCT 20. Moreover, accurate histological examination
should include the assessment of proliferation markers,
with particular regard to the Ki67-labelling index; nuclear
antigen Ki67 is expressed during every phase of the cell
cycle except G0 and, therefore, it can represent an important predictive factor 21. In malignant GCTs, the Ki67-
Fig. 3. On immunohistochemistry, tumour cells were positive for pS100
(a) and CD68/PGM1 (b). Staining for desmin (c) confirmed the presence of
bundles of striated muscle entrapped between neoplastic cells. The Ki67index was very low, close to 0% (d). All pictures were originally taken at 200
magnification.
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index is usually > 10% 20. In our case, the presence of
hyperchromatic, but typical nuclei, abundant cytoplasm,
lack of mitotic figures, and very low Ki67-index (close
to 0%) ruled out an aggressive behaviour and the lesion
was hence diagnosed as benign GCT (Fig. 3). It should be
emphasized that a definitive diagnosis of GCT can only
be made following accurate histological examination, and
that the risk of recurrence is strongly influenced by the
status of the surgical margins 19 22, which, in our case, were
tumour-free. After surgery, long-term follow-up should be
started, because of the risk of local or distant recurrence
even several years after surgery 12. The recurrence rate is
very variable, ranging from 2-50%, depending on surgical radicality and on the presence of infiltrative growth
pattern 23.
Conclusions
Despite its low prevalence, GCT should be considered in the
differential diagnosis of oral lesions, particularly when they
are located in the tongue. Differential diagnosis between
GCT and several other benign and malignant neoplasms,
eventually showing granular cell features, such as smooth
muscle, vascular, fibrohistiocytic, true histiocytic, and
melanocytic tumours, is extremely important with regard to
treatment and prognosis 20. In this setting, complete surgical
removal of the tumour must be attempted, given the possibility of GCT to recur, and histological examination is the
only way to assess the biological behaviour. Histochemistry
and immunohistochemistry can confirm the diagnosis of
GCT when S100-positive cells containing PAS-positive and
CD68-reactive granules are seen 1 24. Adverse immunohistochemical prognostic factors of GCTs include Ki67-index
> 10% and p53 immunoreactivity 20. In the present case, we
did not find any histological criterion of malignancy, and,
not unlike the findings of Chrysomali et al. 21, the Ki67index was very low, resulting positive only in occasional
cells. Albeit, several cases of local and distant recurrence,
even many years after excision of the primary tumour,
have been reported in the literature, hence these lesions
require long-term follow-up.
In conclusion, we suggest that every oral lesion of unknown nature should undergo physical examination and/
or appropriate imaging to reveal the clinical extension of
the disease, and then, when feasible, surgically removed.
The excision should be wide enough to ensure oncological radicality and accurate histological examination of
the specimen; when granular cells are seen on histology, an appropriate immunohistochemical panel should
be applied in order to assess the histological derivation
and proliferative index of the tumour. Further clinical
management can vary depending on the final histological diagnosis: when GCT is diagnosed, close follow-up
should be planned in order to prevent any relapse. Anyway, morphological criteria and the Ki67-index can of-
Granular cell tumour of the tongue in a 14-year-old boy
fer important prognostic information which allows the
clinician to predict the biological behaviour and the risk
of recurrence and to avoid emotional discomfort to the
patient, when no histological criteria of malignancy are
observed and the proliferative index is low (Ki67-index
<10%).
References
1
Ayadi L, Khabir A, Fakhfakh I, et al. Granular cell tumor.
Rev Stomatol Chir Maxillofac 2008;109:158-62.
2
Mohamad Zaini Z, Farah CS. Oral granular cell tumor of the
lip in an adult patient. Oral Oncol EXTRA 2006;2:109-11.
3
Pearse AGE. The histogenesis of granular cell myoblastoma
(granular cell perineural fibroblastoma). J Pathol Bacteriol
1950;62:351-62.
4
Murray MR. Cultural characteristics of three granular cell
myoblastomas. Cancer 1951;5:857-67.
5
Fisher ER, Wechsler H. Granular cell myoblastoma as
misnomer. EM and histochemical evidence concerning its
Schwann cell derivation and nature (granular cell schwannoma). Cancer 1962:15:936.
6
Eversole LR, Sabes WR. Granular sheath cell lesions: report
of cases. J Oral Surg 1971;29:867-71.
7
Zangari F, Trombelli L, Calura G. Granular cell myoblastoma. Review of the literature and report of a case. Minerva
Stomatol 1996;45:231-7.
8
Arevalo C, Maly B, Eliashar R, et al. Laryngeal granular cell
tumor. J Voice 2008;22:339-42.
9
Vered M, Carpenter WM, Buchner A. Granular cell tumor of
the oral cavity: update immunohistochemical profile. J Oral
Pathol Med 2009;38:150-9.
10
Sierra M, Sebag F, De Micco C, et al. Tumeur d’Abrikossoff
de l’oesophage cervical: une cause rare de faux nodule thyroïdien. Ann Chir 2006;131:219-21.
11
Sargenti-Neto S, Brazão-Silva MT, do Nascimento Souza
KC, et al. Multicentric granular cell tumor: report of a patient with oral and cutaneous lesions. Br J Oral Maxillofac
Surg 2009;47:62-4.
er 092 AAOMS. J Oral Maxillofac Surg 2007;65(9s1):4355.
14
Nagaraj PB, Ongole R, Bhujanga-Rao BR. Granular cell tumor of the tongue in a 6-year-old girl - a case report. Med
Oral Patol Oral Cir Bucal 2006;11:E162-4.
15
Giuliani M, Lajolo C, Pagnoni M, et al. Tumore a cellule
granulari della lingua (tumore di Abrikossoff). Presentazione di un caso clinico e revisione della letteratura. Minerva
Stomatol 2004;53:465.
16
Ordonez NG. Granular cell tumor: a review and update. Adv
Anat Pathol 1999;6:186-203.
17
Lacroix-Triki M, Rochaix P, Marques B, et al. Granular cell
tumors of the skin of non-neural origin: report of 8 cases.
Ann Pathol 1999;19:94-8.
18
Senoo H, Iida S, Kishino M, et al. Solitary congenital granular cell lesion of the tongue. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 2007;104:e45-8.
19
Junquera LM, de Vincente JC, Vega JA, et al. Granular-cell
tumours: an immunohistochemical study. Br J Oral Maxillofac Surg 1997;35:180-4.
20
Fanburg-Smith JC, Meis-Kindblom JM, Fante R, et al. Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. Am J Surg Pathol
1998;22:779-94.
21
Chrysomali E, Nikitakis NG, Tosios K, et al. Immunohistochemical evaluation of cell proliferation antigen Ki-67
and apoptosis-related proteins Bcl-2 and caspase-3 in
oral granular cell tumor. Oral Surg Oral Med Oral Pathol
2003;96:566-71.
22
Becelli R, Perugini M, Gasparini G, et al. Abrikossoff’s tumor. J Craniofacial Surg 2001;12:78-81.
12
Leboulanger N, Rouillon I, Papon JF, et al. Childhood granular cell tumors: two case reports. Int J Pediatr Otorhinolaryngol 2008;72:279-83.
23
Sidwell RU, Rouse P, Owen RA, et al. Granular cell tumor of
the scrotum in a child with Noonan syndrome. Pediatr Dermatol 2008;25:341-3.
13
Nakamura K, Sekiya W, Yamada R, et al. A case of granular
cell tumor that developed (originated) in the tongue, Post-
24
An JS, Han SH, Hwang SB, et al. Granular cell tumors of the
abdominal wall. Yonsei Med J 2007;48:727-30.
Received: May 6, 2009 - Accepted: February 4, 2010
Address for correspondence: Dr.ssa C. Carcuscia, E-mail: [email protected]
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